Antiviral Activity of Interferon Alpha-2b and Taurine Combination Against SARS-CoV-2 in vitro.

Interferons (IFN) have antiviral activity against many viruses, including SARS-CoV-2. A combination of IFN-a2b and the antioxidant taurine is widely used in the Russian Federation, and its antiviral activity has not been studied before. The aim of this study was to determine the antiviral activity of interferon drugs, in combination with taurine and without it. The study included cytotoxicity and antiviral activity assays of IFN-a2b preparations, when stored according to the instructions at 2-8degreeC, and after 1 month storage at the temperature of 20-26degreeC in a pre-opened state. The combination of IFN alpha-2b with taurine has a higher antiviral activity compared to IFN alpha-2b mono-preparation by more than 25% at a <<low>> and 85% at a <<high>> multiplicity of infection. Selectivity index for combinations of IFN-a2b (50,000 IU/dose) + taurine (1 mg/ml) and IFN-a2b (10,000 IU/ml) + taurine (0.8 mg/ml) was more than 600 units, whereas for the IFN-a2b (10,000 IU/ml) it was 200 units. Antiviral activity does not change after one month at room temperature. The combination of interferon with taurine at high concentrations was less toxic than interferon. The results obtained demonstrate practicability of interferon alpha-2b and taurine combination use for treatment and prevention of COVID-19.Copyright © Team of Authors, 2022.

URINARY BIOMARKER ANALYSES ON JAPANESE, MEDITERRANEAN AND EURO-WESTERN POPULATIONS: WHICH IS BETTER FOR POSTPANDEMIC LONGEVITY?

Objective: Since nutrition could extend lifespan even in stroke-prone rats developing stroke genetically, our WHO-Collaborating Center for Primary Prevention of Cardio-vascular Diseases (CVD) started world-wide hearth examination to investigate nutrition good for healthy longevity by collecting 24-hour urine (24U) samples. Design: Urinary biomarkers of nutritions, sodium for salt, potassium (K) for vegetables and fruits, isoflavones(Is) for soy, taurine(Ta) for fish and magnesium (Mg) for beans and nuts were analyzed in 24U among 4211 participants (49.7% females(F)), aged 48-56 years in 50 populations from 22 countries according to WHO-CARDIAC(Cardiovascular Diseases and Alimentary Compression) Study Protocol, and studied comparatively in 6 Japanese(J), 6 Mediterranean(M) populations from Greece, Italy(2), Spain(2), Portugal and 6 Euro-Western(EW) populations from Sweden, Ireland, Scotland, Canada, Australia, New Zealand. Results with Discussion: The quintile analyses of Ta and Mg/creatine ratio in the world were inversely associated with CVD risks. The Odds ratios of obesity, hypercholesterolemia and hypertension in the lowest quintile of both Ta and Mg were 6.3, 4.6 and 1.8, respectively. J and M populations had significantly higher Ta and Mg therefore, lower CVD risks than EW, but J and M took more salt increasing the risk of stroke (Table 1). Despite the high salt intake, M had the merit of significantly high K intake to attenuate the adverse salt effect. J had a merit to take Is from soy containing Mg. Since Is intake was inversely associated with lower BMI in the world populations, high Japanese Mg intake was related to high Is intake which was inversely associated with obesity in Japan. In fact, the Japanese populations who took significantly higher T and Mg had lower BMI as well as higher HDL and folic acid in the blood, expected to prevent atherosclerosis and dementia. In contrast to M and EW, particularly severe obesity over BMI 30 was obviously less in J, ranking 182nd among 190 populations (WHO). The mortality rates of COVID-19 were significantly positively related to the ratio of severe obesity among 20 major countries in the world and this mortality was obviously lower in J, suggestive of the potential of J diet for post-pandemic longevity. Conclusion: 24U biomarker analyses indicated low-salted J and M diets are recommendable for CVD prevention. J diet is so far better than M diet because of lower CVD risks such as obesity and lipidemia, which were proven by urinary biomarkers to be related with traditional fish and soy intakes.

Antiviral Activity of Interferon Alpha-2b and Taurine Combination Against SARS-CoV-2 in vitro

Interferons (IFN) have antiviral activity against many viruses, including SARS-CoV-2. A combination of IFN-a2b and the antioxidant taurine is widely used in the Russian Federation, and its antiviral activity has not been studied before. The aim of this study was to determine the antiviral activity of interferon drugs, in combination with taurine and without it. The study included cytotoxicity and antiviral activity assays of IFN-a2b preparations, when stored according to the instructions at 2-8°C, and after 1 month storage at the temperature of 20-26°C in a pre-opened state. The combination of IFN alpha-2b with taurine has a higher antiviral activity compared to IFN alpha-2b mono-preparation by more than 25% at a «low» and 85% at a «high» multiplicity of infection. Selectivity index for combinations of IFN-a2b (50,000 IU/dose) + taurine (1 mg/ml) and IFN-a2b (10,000 IU/ml) + taurine (0.8 mg/ml) was more than 600 units, whereas for the IFN-a2b (10,000 IU/ml) it was 200 units. Antiviral activity does not change after one month at room temperature. The combination of interferon with taurine at high concentrations was less toxic than interferon. The results obtained demonstrate practicability of interferon alpha-2b and taurine combination use for treatment and prevention of COVID-19.

Current Opinion on the Therapeutic Capacity of Taurine-Containing Halogen Derivatives in Infectious and Inflammatory Diseases.

Taurine haloamines, N-chlorotaurine (NCT, TauCl), and N-bromotaurine (NBT, TauBr) are formed by a reaction between taurine and hypohalous acids, HOCl and HOBr, respectively. The major source of endogenous taurine haloamines is neutrophils. Both NCT and NBT share strong anti-inflammatory and microbicidal activities supported by an absence of microbial resistance. In the light of these properties, a number of clinical studies have been performed to document their effectiveness in treatment of bacterial, fungal, and viral infections. The administration of NCT and NBT has been limited to topical application, as they are decomposed upon systemic delivery. This review summarizes current knowledge concerning the therapeutic use of NCT and NBT mainly in various skin disorders such as non-healing wounds, acne vulgaris, herpes zoster, and psoriasis. Moreover, the beneficial effect of NCT inhalation in early stages of COVID-19 and other viral respiratory infections is discussed. And finally, we would like to suggest that NCT might be used to inhibit the development of the cytokine storm through its capacity to suppress the production of IL-6.

Examination of Taurine Chloramine and Taurine on LPS-Induced Acute Pulmonary Inflammatory in Mice.

The novel coronavirus disease (COVID-19), which is prevalent in the world, develops severe pneumonia, of which 30% have fatal acute respiratory distress and acute lung injury. At present, there is no established treatment method for ARDS, and it is desired to develop a therapeutic drug as soon as possible. While TauCl has been reported to have anti-inflammatory effects on culture cells, little information is available concerning in vivo experiments. In the present study, we evaluated the anti-inflammatory effect of taurine chloramine (TauCl), a taurine derivative, against LPS-induced pneumonia in mouse. The mice were pretreated with TauCl intraperitoneally before intratracheal administration of LPS. Additionally, we evaluated the effect of taurine treatment by maintaining the mice on drinking water containing 0.5% taurine. Two days after LPS injection, body weight was decreased by 9.5 %, while lung weight was increased due to the infiltration of inflammatory cells; TauCl attenuated the gain in lung weight. LPS-induced acute pneumonia caused an increase in cytokine/chemokine mRNA expression, including that of IL-1ß, -6, -17, TNF-α, and MCP-1. However, TauCl treatment attenuated IL-6 expression, but not that of the others although the induction of plasma IL-6 tended to be reduced by TauCl treatment. Importantly, a similar effect against LPS-induced acute lung inflammation was confirmed by taurine pretreatment. These findings suggest that TauCl treatment partially prevents IL-6 production induced by acute pneumonia in vivo.

The Disease-Modifying Role of Taurine and Its Therapeutic Potential in Coronavirus Disease 2019 (COVID-19).

Taurine is an amino sulfonic acid that is implicated in numerous physiological functions, including the regulation of oxidative stress, which plays an important role in coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), together with other pathophysiological processes. The recent finding of decreased serum taurine levels in SARS-CoV-2-infected patients, in tandem with its potential modulatory role in COVID-19 due to its antiviral, antioxidant, anti-inflammatory, and vascular-related effects, provides a rationale for considering taurine as a beneficial supplement in patients suffering from COVID-19. Here, we reviewed the potential disease-modifying effects of taurine and combined these with the current knowledge on COVID-19 to clarify the potential role of taurine in this respiratory disease.

Central Taurine Attenuates Hyperthermia and Isolation Stress Behaviors Augmented by Corticotropin-Releasing Factor with Modifying Brain Amino Acid Metabolism in Neonatal Chicks.

The objective of this study was to determine the effects of centrally administered taurine on rectal temperature, behavioral responses and brain amino acid metabolism under isolation stress and the presence of co-injected corticotropin-releasing factor (CRF). Neonatal chicks were centrally injected with saline, 2.1 pmol of CRF, 2.5 µmol of taurine or both taurine and CRF. The results showed that CRF-induced hyperthermia was attenuated by co-injection with taurine. Taurine, alone or with CRF, significantly decreased the number of distress vocalizations and the time spent in active wakefulness, as well as increased the time spent in the sleeping posture, compared with the saline- and CRF-injected chicks. An amino acid chromatographic analysis revealed that diencephalic leucine, isoleucine, tyrosine, glutamate, asparagine, alanine, ß-alanine, cystathionine and 3-methylhistidine were decreased in response to taurine alone or in combination with CRF. Central taurine, alone and when co-administered with CRF, decreased isoleucine, phenylalanine, tyrosine and cysteine, but increased glycine concentrations in the brainstem, compared with saline and CRF groups. The results collectively indicate that central taurine attenuated CRF-induced hyperthermia and stress behaviors in neonatal chicks, and the mechanism likely involves the repartitioning of amino acids to different metabolic pathways. In particular, brain leucine, isoleucine, cysteine, glutamate and glycine may be mobilized to cope with acute stressors.

N-Acetylcysteine and Hydrogen Sulfide in Coronavirus Disease 2019.

Significance: Hydrogen sulfide (H2S) is one of the three main gasotransmitters that are endogenously produced in humans and are protective against oxidative stress. Recent findings from studies focusing on coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), shifted our attention to a potentially modulatory role of H2S in this viral respiratory disease. Recent Advances: H2S levels at hospital admission may be of importance since this gasotransmitter has been shown to be protective against lung damage through its antiviral, antioxidant, and anti-inflammatory actions. Furthermore, many COVID-19 cases have been described demonstrating remarkable clinical improvement upon administration of high doses of N-acetylcysteine (NAC). NAC is a renowned pharmacological antioxidant substance acting as a source of cysteine, thereby promoting endogenous glutathione (GSH) biosynthesis as well as generation of sulfane sulfur species when desulfurated to H2S. Critical Issues: Combining H2S physiology and currently available knowledge of COVID-19, H2S is hypothesized to target three main vulnerabilities of SARS-CoV-2: (i) cell entry through interfering with functional host receptors, (ii) viral replication through acting on RNA-dependent RNA polymerase (RdRp), and (iii) the escalation of inflammation to a potentially lethal hyperinflammatory cytokine storm (toll-like receptor 4 [TLR4] pathway and NLR family pyrin domain containing 3 [NLRP3] inflammasome). Future Directions: Dissecting the breakdown of NAC reveals the possibility of increasing endogenous H2S levels, which may provide a convenient rationale for the application of H2S-targeted therapeutics. Further randomized-controlled trials are warranted to investigate its definitive role.

The serum amino acid profile in COVID-19.

The pandemic of the coronavirus disease (COVID-19) caused by SARS-CoV-2 affects millions of people worldwide. There are still many unknown aspects to this infection which affects the whole world. In addition, the potential impacts caused by this infection are still unclear. Amino acid metabolism, in particular, contains significant clues in terms of the development and prevention of many diseases. Therefore, this study aimed to compare amino acid profile of COVID-19 and healthy subject. In this study, the amino acid profiles of patients with asymptomatic, mild, moderate, and severe/critical SARS-CoV-2 infection were scanned with LC-MS/MS. The amino acid profile encompassing 30 amino acids in 142 people including 30 control and 112 COVID-19 patients was examined. 20 amino acids showed significant differences when compared to the control group in COVID-19 patient groups with different levels of severity in the statistical analyses conducted. It was detected that the branched-chain amino acids (BCAAs) changed in correlation with one another, and L-2-aminobutyric acid and L-phenylalanine had biomarker potential for COVID-19. Moreover, it was concluded that L-2-aminobutyric acid could provide prognostic information about the course of the disease. We believe that a new viewpoint will develop regarding the diagnosis, treatment, and prognosis as a result of the evaluation of the serum amino acid profiles of COVID-19 patients. Determining L-phenylalanine and L-2-aminobutyric levels can be used in laboratories as a COVID-19-biomarker. Also, supplementing COVID patients with taurine and BCAAs can be beneficial for treatment protocols.